International Journal of Molecular and Cellular Medicineمجله بین المللی سلولی و مولکولیInt J Mol Cell MedMedical Scienceshttp://ijmcmed.org1admin2251-96372251-964510.22088/IJMCM.BUMSenjalali139751gregorian20188173online1fulltextenInhibition of Interleukin-1 Receptor-Associated Kinases 1/4, Increases Gene Expression and Serum Level of Adiponectin in Mouse Model of Insulin ResistanceClinical BiochemistryClinical BiochemistryOriginal ArticleOriginal Article<div style="text-align: justify;">Insulin resistance is a feature of most patients with type 2 diabetes mellitus. Epidemiological evidence suggests a correlation between inflammation and insulin resistant states such as obesity, but the underlying mechanisms are largely unknown. Interleukin-1 receptor-associated kinases (IRAK) play a central role in inflammatory responses by regulating the expression of various inflammatory genes in immune cells. This study was aimed to investigate the effect of IRAK inhibitor on gene transcription and serum concentration of adiponectin in insulin-resistant mice. Experimental mice were randomly divided into 6 groups: the healthy control group was fed a regular chow diet while other groups were fed with a high-fat diet for 12 weeks. After this period, animals were treated with IRAK inhibitor, pioglitazone, both IRAK and pioglitazone, and DMSO, for two weeks. Adiponectin gene expression level was analyzed by real-time PCR. Additionally, serum adiponectin levels were measured by ELISA. Homeostasis model assessment-adiponectin (HOMA-AD) as an insulin sensitivity index was calculated. IRAK inhibitor and pioglitazone increased significantly the expression of adiponectin gene. Also, adiponectin concentration in the control group (9.67&plusmn;1.1 &mu;g/ml) increased to 25.34&plusmn;2.04 &mu;g/ml in pioglitazone treatment group. IRAK inhibitor also increased adiponectin concentration (18.24&plusmn;1.53 &mu;g/ml) but did not show a synergistic effect with pioglitazone when administered simultaneously (26.66&plusmn;2.5 &mu;g/ml). &nbsp;HOMA-AD was 0.33&plusmn;0.04 in the pioglitazone-treated group, 0.6&plusmn;0.13 in IRAK inhibitor group, and 0.31&plusmn;0.03 in animals that received IRAKi and pioglitazone. &nbsp;Our findings suggest that increased adiponectin secretion from adipose tissue mediated by IRAK inhibitor may increase the insulin sensitivity in an animal model of insulin resistance.</div>
Insulin resistance, Inflammation, Adiponectin, IRAK inhibitor185192http://ijmcmed.org/browse.php?a_code=A-10-1561-1&slc_lang=en&sid=1AthenaRajaiea.rajaienejad@gmail.com100319475328460012658100319475328460012658NoDepartment of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.MostafaAllahyarimostafa.allah1993@gmail.com100319475328460012659100319475328460012659NoDepartment of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.MahdiehNazari-Robatimn_robati@yahoo.com100319475328460012660100319475328460012660NoDepartment of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.HosseinFallahhf59ma@gmail.com100319475328460012661100319475328460012661Yes
Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.